Design and Characterization of Temozolomide-Loaded Ethosomal Hydrogel

Cutaneous melanoma is a highly aggressive skin cancer associated with poor targeting and systemic toxicity of conventional chemotherapy. This study aimed to develop and evaluate a temozolomide-loaded ethosomal hydrogel for enhanced localized transdermal delivery. Ethosomes were formulated using the ethanol injection method and optimized using Design of Experiments (DoE) software, followed by incorporation into a sodium carboxymethyl cellulose-based hydrogel.Preformulation studies, including UV–visible spectroscopy and FTIR analysis, confirmed drug identity and compatibility with excipients. The optimized ethosomes were characterized using a zeta sizer for particle size, polydispersity index (PDI), and zeta potential, demonstrating nanoscale size, narrow distribution, and good stability. Transmission electron microscopy (TEM) confirmed spherical vesicle morphology. High entrapment efficiency and sustained drug release were observed.The ethosomal hydrogel exhibited desirable physicochemical properties such as appropriate pH, viscosity, spreadability, and uniform drug content. In-vitro diffusion studies showed enhanced skin permeation, while cytotoxicity (MTT assay) demonstrated improved anticancer activity.Overall, the developed system offers a promising nanocarrier-based strategy for targeted and sustained delivery of temozolomide in melanoma therapy, with potential to reduce systemic toxicity and improve therapeutic outcomes.